Variant rs3217986 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004936.4(CDKN2B):c.*656A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0877 in 238,184 control chromosomes in the GnomAD database, including 1,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.087 ( 966 hom., cov: 32)

Exomes 𝑓: 0.089 ( 484 hom. )

Consequence

CDKN2B
NM_004936.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -0.659

Variant links:

Genes affected

CDKN2B (HGNC:1788): (cyclin dependent kinase inhibitor 2B) This gene lies adjacent to the tumor suppressor gene CDKN2A in a region that is frequently mutated and deleted in a wide variety of tumors. This gene encodes a cyclin-dependent kinase inhibitor, which forms a complex with CDK4 or CDK6, and prevents the activation of the CDK kinases, thus the encoded protein functions as a cell growth regulator that controls cell cycle G1 progression. The expression of this gene was found to be dramatically induced by TGF beta, which suggested its role in the TGF beta induced growth inhibition. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

CDKN2B links:

CDKN2B-AS1 (HGNC:34341): (CDKN2B antisense RNA 1) This gene is located within the CDKN2B-CDKN2A gene cluster at chromosome 9p21. The gene product is a functional RNA molecule that interacts with polycomb repressive complex-1 (PRC1) and -2 (PRC2), leading to epigenetic silencing of other genes in this cluster. This region is a significant genetic susceptibility locus for cardiovascular disease, and has also been linked to a number of other pathologies, including several cancers, intracranial aneurysm, type-2 diabetes, periodontitis, Alzheimer's disease, endometriosis, frailty in the elderly, and glaucoma. Multiple alternatively processed transcript variants have been detected, some of which may take the form of circular RNA molecules (PMID:21151960). [provided by RefSeq, May 2014]

CDKN2B-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN2B	NM_004936.4 linkuse as main transcript	c.*656A>C		3_prime_UTR_variant	2/2	ENST00000276925.7
CDKN2B-AS1	NR_003529.3 linkuse as main transcript	n.371+10170T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN2B	ENST00000276925.7 linkuse as main transcript	c.*656A>C		3_prime_UTR_variant	2/2	1	NM_004936.4	P1	P42772-1
CDKN2B-AS1	ENST00000650946.1 linkuse as main transcript	n.29+10170T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0867

AC:

13188

AN:

152054

Hom.:

968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0203

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.0901

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0856

Gnomad OTH

AF:

0.0915

GnomAD4 exome

AF:

0.0894

AC:

7689

AN:

86012

Hom.:

484

Cov.:

AF XY:

0.0888

AC XY:

3523

AN XY:

39688

show subpopulations

Gnomad4 AFR exome

AF:

0.0173

Gnomad4 AMR exome

AF:

0.298

Gnomad4 ASJ exome

AF:

0.0870

Gnomad4 EAS exome

AF:

0.0591

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.0849

Gnomad4 NFE exome

AF:

0.0857

Gnomad4 OTH exome

AF:

0.0938

GnomAD4 genome

AF:

0.0867

AC:

13188

AN:

152172

Hom.:

966

Cov.:

AF XY:

0.0916

AC XY:

6811

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0202

Gnomad4 AMR

AF:

0.239

Gnomad4 ASJ

AF:

0.0781

Gnomad4 EAS

AF:

0.0897

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.0856

Gnomad4 OTH

AF:

0.0905

Alfa

AF:

0.0949

Hom.:

1126

Bravo

AF:

0.0952

Asia WGS

AF:

0.138

AC:

478

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Three Vessel Coronary Disease

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

1.3

Dann

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over